Typically, bags of solutions for intravenous injection of patients are prepared manually by pharmacists or pharmacist's aides. Each solution must be tailored to the particular needs of the patient with respect to composition, quantity and type of medicament, and pH level. Variations from required levels can have deleterious, even fatal, consequences for the patient. Pharmacists and their assistants are highly trained and conscientious professionals. Nonetheless, under the pressures of time and environment, these professionals can make errors. In addition, the need to keep the final preparation sterile requires costly and time-consuming measures on the part of those who prepare the solutions.
Heat sterilization of solutions for intravenous injection, for example as part of a total parenteral nutrition system can lead to carmelization of the injectable sugars, which can have enormously negative consequences for the health of the patient.
In my prior U.S. Pat. No. 4,906,103 I disclosed a system for the cold sterilization of solutions which completely avoids the hazards of heat sterilization. In my prior U.S. Pat. No. 5,196,001 I disclosed a preparation assembly and unit dose medicament containers for use in a cold sterilization system which permitted controlled pre-preparation dosing of medicaments.
Since the introduction of Total Parenteral Nutrition (TPN), manufacturers have not been able to overcome the chemical incompatibility of the glucose solution with the amino acid solution, due to the Maillard reaction. Hence, the glucose and amino acid solutions have had to be bottled separated at the manufacturer, and then prepared as the TPN solution in the hospital's Intravenous Admixture Room at substantial cost to the patient.
The conventional heat sterilization process has a number of drawbacks which are overcome by the use of cool sterilization. Among the problems with heat sterilization are:
1. Inverted sugar and dextrose injectibles have a neutral pH, however heat sterilization makes these injectibles acidic with a carmelization of the sugar and the dextrose.
2. When the solution is heated in the container, be it glass or plastic, the container material goes into solution with the heated liquids and reacts with the chemical solution to form particulate matter. Particulate matter is undesirable in an injected substance.
3. Heat sterilization produces 5-hydroxymethylfurfural and related substances which are highly acidic and poisonous degraded impurities from sugar.
By using cool sterilization, the upper and lower limitation of percentage of sugars can be narrowed down into a controllable range. Because the 5-hydroxymethylfurfural and hydroxymethylfurfural from fructose are not produced in the cool sterilization process, it is expected that it will be possible to maintain the purity of the sugars in a range better than the U.S. Pharmacopeia's range for heat sterilization of 95 percent to 105 percent.
Great strides have been made in automatic dispensing of solid pills and powders by way of computer controlled robotic assemblies. With greater attention to costs at all levels of the health care system, efforts have been made to limit the direct intervention of doctors and pharmacists in dispensing of medications, while at the same time maintaining adequate control by these professionals. Solid pills and capsules are by their nature suited to dispensing in unit doses, but the remotely operated drawers and dispensers which are adequate for pills are not effective for the preparation of individualized injectable solutions. Furthermore, robotic devices for dispensing liquids from a storage vessel of liquid present serious concerns in the preparation of solutions for administration to humans. Typically an aliquot of liquid would be dispensed by a micropump. Yet pumps are subject to malfunctions, and great care needs to be taken to quality check whether the desired quantity of liquid has actually been dispensed. In any event, no physical record remains to verify the amount and type of liquid dispensed. What is needed is a consistent and effective apparatus for preparing and dispensing liquid medicament solutions.
With the expanded exploration and commercialization of remote regions, both on earth and in space, before long many workers and explorers will be stationed at distant outposts far from the aid or intervention of licensed pharmacists and physicians. Nevertheless, these pioneers are placed at their posts at great cost, and represent a tremendous investment in training, capital, and transportation. Should such an isolated worker become ill or injured, the finest health care and medical intervention will be called for. What is needed is a system for providing the intravenous injectable solutions which can be controlled by skilled professions far removed from the site of injection.